Rescaling creatinine makes GFR estimation equations generally applicable across populations - validation results for the Lund-Malmö equation in a French cohort of sub-Saharan ancestry.

OBJECTIVES: To make glomerular filtration rate (GFR) estimating equations applicable across populations with different creatinine generation by using rescaled serum creatinine (sCr/Q) where sCr represents the individual creatinine level and Q the average creatinine value in healthy persons of the same population. METHODS: GFR measurements (mGFR, plasma clearance of 51Cr-EDTA) were conducted in 964 adult Black Europeans. We established the re-expressed Lund-Malmö revised equation (r-LMR) by replacing serum creatinine (sCr) with rescaled creatinine sCr/Q. We evaluated the r-LMR equation based on Q-values of White Europeans (r-LMRQ-white; Q-values females: 62 µmol/L, males: 80 µmol/L) and Black Europeans (r-LMRQ-Black; Q-values females: 65 µmol/L, males: 90 µmol/L), and the European Kidney Function Consortium equation (EKFCQ-White and EKFCQ-Black) regarding bias, precision (interquartile range, IQR) and accuracy (percentage of estimates within ±10 % [P10] and ±30 % [P30] of mGFR). RESULTS: Median bias of r-LMRQ-White/r-LMRQ-Black/EKFCQ-White/EKFCQ-Black were -9.1/-4.5/-6.3/-0.9 mL/min/1.73 m2, IQR 14.7/14.5/14.5/15.6 mL/min/1.73 m2, P10 25.1 %/34.8 %/30.3 %/37.2 % and P30 74.2 %/84.1 %/80.6 %/83.6 %. The improvement of bias and accuracy when using proper Q-values was most pronounced in men. Similar improvements were obtained above and below mGFR 60 mL/min/1.73 m2 and at various age and BMI intervals, except for BMI<20 kg/m2 where bias increased, and accuracy decreased. CONCLUSIONS: GFR estimating equations may be re-expressed to include rescaled creatinine (sCr/Q) and used across populations with different creatinine generation if population-specific average creatinine concentrations (Q-values) for healthy persons are established.

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50 µmol/L; ≥80 years, 54.41-96.43 µmol/L. RIs for females were: 18-59 years, 40.42-69.73 µmol/L; 60-79 years, 41.16-73.69 µmol/L; ≥80 years, 46.50-73.20 µmol/L. Q-values were set at 73.82 µmol/L (0.84 mg/dL) for males and 53.80 µmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

Primary sclerosing cholangitis causally affects kidney function decline: A Mendelian randomization study.

BACKGROUND AND AIM: The causal linkage between primary sclerosing cholangitis (PSC) and kidney function is unexplored despite their potential for long-term detrimental effects on kidney function. METHODS: Two-sample summary-level Mendelian randomization (MR) study was conducted to identify the association between PSC and kidney function. The genetic variants were extracted from the PSC-specific multi-trait analyzed genome-wide association study (GWAS) of European ancestry. Summary-level data for kidney function traits, including estimated glomerular filtration rate (eGFR), annual eGFR decline, and chronic kidney disease (CKD), were obtained from the CKDGen consortium. Multiplicative random-effects inverse-variance weighted (MR-IVW), and a series of pleiotropy-robust analyses were performed to investigate the causal effects and ascertain their robustness. RESULTS: Significant causal associations between genetically predicted PSC and kidney function traits were identified. Genetically predicted PSC was associated with decreased log-transformed eGFR (MR-IVW; beta = -0.41%; standard error [SE] = 0.02%; P < 0.001), increased rate of annual eGFR decline (MR-IVW; beta = 2.43%; SE = 0.18%; P < 0.001), and higher risk of CKD (MR-IVW; odds ratio = 1.07; 95% confidence interval = 1.06-1.08; P < 0.001). The main findings were supported by pleiotropy-robust analysis, including MR-Egger with bootstrapped error and weighted median. CONCLUSIONS: Our study demonstrates that genetically predicted PSC is causally associated with kidney function impairment. Further studies are warranted to identify the underlying mechanisms.

[Functional and oncologic outcomes of partial nephrectomy for cystic renal cell carcinoma: A single-center retrospective study].

OBJECTIVE: To investigate the postoperative renal function and oncologic outcomes of cystic renal cell carcinoma with partial nephrectomy, and to compared the single-center data on surgical outcomes with the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: This was a retrospective study that included the patients with cystic renal cell carcinoma who underwent partial nephrectomy in the Department of Urology, Peking University Third Hospital (PUTH) from 2010 to 2023. The clinical data and depicting baseline characteristics were collected. Renal dynamic imaging and the Chinese Coefficients for Chronic Kidney Disease Epidemiology Collaboration (C-CKD-EPI) formulae were used to calculate the estimated glomerular filtration rate (eGFR). The renal function curves over time were then plotted, and the patients were followed-up to record their survival status. Cases of cystic renal cell carcinoma in the SEER database between 2000 and 2020 were included, propensity score matching (PSM) was performed to balance the differences between SEER cohort and PUTH cohort, and the cancer-specific survival (CSS) curves for both groups were plotted and statistical differences were calculated by the Kaplan-Meier method. RESULTS: A total of 38 and 385 patients were included in the PUTH cohort and SEER cohort, respectively, and 31 and 72 patients were screened in each cohort after PSM. Of the baseline characteristics, only tumor size (P=0.042) was found to differ statistically between the two groups. There was no statistically significant difference between the two cohorts in terms of CSS after PSM (P=0.556). The median follow-up time in the SEER cohort was 112.5 (65, 152) months and a 10-year survival rate of 97.2%, while the PUTH cohort had a median follow-up of 57.0 (20, 1 172) months and a 10-year survival rate of 100.0%. There was no statistically significant difference between eGFR determined by preoperative renal dynamic imaging and the results of the C-CKD-EPI formulae based on creatinine estimation (P=0.073). There was a statistically significant difference in eGFR among the preoperative, short-term postoperative, and long-term postoperative (P < 0.001), which was characterized by the presence of a decline in renal function in the short-term postoperative period and the recovery of renal function in the long-term period. CONCLUSION: Partial nephrectomy for cystic renal cell carcinoma is safe and feasible with favorable renal function and oncologic outcomes.

Allometric body shape indices, type 2 diabetes and kidney function: A two-sample Mendelian randomization study.

AIM: To examine the association between body mass index (BMI)-independent allometric body shape indices and kidney function. MATERIALS AND METHODS: We performed a two-sample Mendelian randomization (MR) analysis, using summary statistics from UK Biobank, CKDGen and DIAGRAM. BMI-independent allometric body shape indices were: A Body Shape Index (ABSI), Waist-Hip Index (WHI) and Hip Index (HI). Kidney function outcomes were: urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate and blood urea nitrogen. Furthermore, we investigated type 2 diabetes (T2D) as a potential mediator on the pathway to albuminuria. The main analysis was inverse variance-weighted random-effects MR in participants of European ancestry. We also performed several sensitivity MR analyses. RESULTS: A 1-standard deviation (SD) increase in genetically predicted ABSI and WHI levels was associated with higher UACR (ß = 0.039 [95% confidence interval: 0.016, 0.063] log [UACR], P = 0.001 for ABSI, and ß = 0.028 [0.012, 0.044] log [UACR], P = 6 x 10-4 for WHI) in women, but not in men. Meanwhile, a 1-SD increase in genetically predicted HI was associated with lower UACR in women (ß = -0.021 [-0.041, 0.000] log [UACR], P = 0.05) and in men (ß = -0.026 [-0.058, 0.005] log [UACR], P = 0.10). Corresponding estimates in individuals with diabetes were substantially augmented. Risk of T2D increased for genetically high ABSI and WHI in women (P < 6 x 10-19 ) only, but decreased for genetically high HI in both sexes (P < 9 x 10-3 ). No other associations were observed. CONCLUSIONS: Genetically high HI was associated with decreased risk of albuminuria, mediated through decreased T2D risk in both sexes. Opposite associations applied to genetically high ABSI and WHI in women only.

Impact of weight and creatinine adjustments on the accuracy of Cockcroft-gault equation in hematopoietic cell transplant patients.

BACKGROUND: Hematopoietic cell transplant (HCT) patients undergo pre- transplant renal function evaluation to confirm transplant eligibility and tailor pharmacotherapy. There is limited evidence regarding the most accurate method of estimating creatinine clearance (CrCl) within this patient population and no studies exist that evaluate the weight utilized within the Cockcroft-Gault (CG) equation in HCT patients. This study evaluates different weight and serum creatinine (SCr) adjustments utilized within the CG equation estimating for renal clearance in patients undergoing HCT. OBJECTIVE: This is a retrospective, single center analysis of adult HCT patients who underwent pre-transplant evaluation with a measured CrCl using a 24-h urine creatinine collection. The primary outcome was to evaluate the correlation of various weights used in estimation of CrCl compared to measured CrCl. Key secondary outcomes include evaluation of the impact of various weights on estimated CrCl in subpopulations, evaluation of adjusting SCr to pre-determined limits, and determination of an appropriate obesity threshold to utilize body weight adjustments. RESULTS: Seven-hundred and forty-two patients were included in the study. In the primary analysis, CG utilizing adjusted body weight (ADjBW0.4 ) had a greater correlation (r = .812) to measured CrCl when compared to total or ideal body weight (r = .801 and r = .790 respectively). The threshold of 120% of ideal body weight (IBW) produced less bias and greater accuracy in comparison to the threshold of 140% IBW. In patients 60 years or older, rounding low SCr values up .8 or 1 mg/dL resulted in decreased correlation and a greater mean difference in comparison to not rounding SCr. CONCLUSION: In HCT patients who are overweight or obese, ADjBW .4 is the most accurate weight for the CG equation. In HCT patients who have a total body weight < 120% IBW, total body weight is the most accurate weight to utilize. Rounding up low SCr to .8 or 1 mg/dL does not improve the accuracy or led to less bias of the CG equation.

[Clinical Characteristics and Prognosis of Diabetic Foot Ulcers Patients of Different Renal Function Statuses].

Objective: To explore the clinical characteristics and the prognosis of diabetic foot ulcers (DFU) inpatients of different renal function statuses. Methods: A retrospective analysis of 962 inpatients with DFU was conducted. The patients were divided into three groups according to their renal function statuses, and the clinical characteristics of the three groups were compared to identify differences. In addition, the patients were followed up in outpatient clinics or by telephone and their prognostic status and risk factors for death were analyzed. Results: Analysis of the clinical characteristics showed that, compared with diabetic patients with normal renal function or mild renal function impairment, diabetic patients with moderate and severe renal function impairment had a longer course of disease ( P<0.001). Patients with foot ulcers of Wagner grade 4 predominates the moderate and severe renal function impairment groups ( P<0.05). Patients in the moderate and severe renal function impairment groups had a relatively higher proportion of comorbidities, including hypertension, coronary heart disease, and peripheral arterial disease ( P<0.05). These patients had relatively lower levels of glycosylated hemoglobin and hemoglobin (all P<0.05) and relatively higher levels of neutrophil ratio and procalcitonin (all P<0.05). Of the two groups, patients in the moderate renal function impairment group were older ( P<0.001) and had lower ankle-brachial index ( P<0.001). The severe renal function impairment group had a higher proportion of patients with foot ulcers of Wagner grades 3 and 5 (all P<0.05). For the purpose of conducting prognostic analysis, 748 patients were followed up in outpatient clinics or by telephone for a median length of 41 months. Among them, 239 died. The all-cause mortality was 31.9%, and the mortality in the three groups was 25.8%, 46.2% ( P<0.001), and 59.4% ( P<0.001), respectively. The survival rate of patients in the moderate and severe renal function impairment groups was significantly lower than those in the normal renal function and mild renal function impairment groups ( P<0.001). Univariate Cox regression analysis showed that age, concomitant coronary heart disease and peripheral arterial disease, degree of renal function impairment, and foot ulcers of Wagner grade 4 and 5 were associated with all-cause deaths. Furthermore, multivariate Cox regression analysis showed that moderate and severe renal function impairment was an independent risk factor for all-cause deaths in DFU patients ( P<0.001). Conclusions: As renal function impairment worsens, patients with DFU present clinical characteristics of greater complexity, higher risks of cardiovascular events, and higher mortality. It is essential to prevent kidney damage and foot ulcers, to pay attention to the cardiovascular risks of DFU patients with moderate and severe renal function impairment, and to reduce mortality.

Are patients with Covid-19 at risk of long-term chronic kidney disease?

Background: The relationship between Coronavirus Disease 2019 (COVID-19) and acute kidney injury (AKI) is well-established. However, a comprehensive evaluation of kidney outcomes in the long-term course of COVID-19 is not yet been performed. The aim of this study is to investigate whether chronic kidney disease (CKD) develops within six months after hospital discharge in COVID-19 patients who did not have kidney damage at the time of admission to the hospital. Patients and Methods: This single-center retrospective study investigated a total of 1008 participants selected from 7500 COVID-19 patients with real-time reverse transcription-polymerase chain reaction (RT-PCR) positivity. All patients had mild/moderate or severe COVID-19. Patients were randomly selected from inpatient and outpatient settings. Critical COVID-19 patients were not included. Results: The mean age of the patients was 56.57 ± 16.30 years, and 69.9% of them were male. The comorbidity percentages of the participants were as follows; 19.5% coronary artery disease (CAD), 28.6% diabetes mellitus (DM), 36.2% hypertension (HT), 3.1% cerebrovascular obstruction (CVO), 1.7% malignancy, 2.6% chronic obstructive pulmonary disease (COPD), 9.4% asthma, % 1.7 dementia, 9.9% hyperlipidaemia, and 1.7% hepatitis B virus (HBV). Kidney function tests of these patients at first admission and 6 months later were compared to reveal the relationship between COVID-19 and CKD. Serum glucose, sodium estimated glomerular filtration rate (eGFR), and uric acid levels were found to be high in the post-COVID-19 period (P = 0.001). However, there were a decrease in serum albumin, potassium, alanine aminotransferase (ALT), C-reactive protein (CRP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) levels (P = 0.001). The difference between the first measurement of serum urea and creatinine (Cr) levels and the measurement 6 months later was not statistically significant (P = 0.102 and P = 0.300, respectively). Conclusions: Those who survived the mild/moderate and severe clinical manifestations of COVID-19 did not exhibit any risk of kidney outcomes after the acute phase of the disease, suggesting that the kidney can protect itself over a long period of time.

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF.

BACKGROUND: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure). We also examined the effect of dapagliflozin on kidney function after randomization. METHODS: Patients who have HFrEF with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL·min-1·1.73 m-2 were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) according to eGFR category at baseline (<60 and ≥60 mL·min-1·1.73 m-2) and used eGFR at baseline as a continuous measure, as well. Secondary cardiovascular outcomes and a prespecified composite renal outcome (≥50% sustained decline eGFR, end-stage renal disease, or renal death) were also examined, along with a decline in eGFR over time. RESULTS: Of 4742 patients with a baseline eGFR, 1926 (41%) had eGFR <60 mL·min-1·1.73 m-2. The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% CI) for the primary end point in patients with chronic kidney disease was 0.71 (0.59-0.86) versus 0.77 (0.64-0.93) in those with an eGFR ≥60 mL·min-1·1.73 m-2 (interaction P=0.54). The composite renal outcome was not reduced by dapagliflozin (hazard ratio=0.71 [95% CI, 0.44-1.16]; P=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.40 to -0.77) versus placebo -2.85 (-3.17 to -2.53) mL·min-1·1.73 m-2 per year (P<0.001). This was observed in those with and without type 2 diabetes (P for interaction=0.92). CONCLUSIONS: Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF, and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients With Atrial Fibrillation After Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

BACKGROUND: In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. METHODS: In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial. RESULTS: Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min-1·1.73 m-2, respectively. At the 6-month follow-up, a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with vitamin K antagonists, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30 to 50 mL·min-1·1.73 m-2 for bleeding events with rates of 13.1% versus 21.3% (hazard ratio, 0.59; 95% CI, 0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL·min-1·1.73 m-2: 16.6% versus 5.6% (hazard ratio, 3.22; 95% CI, 2.19-4.74; P for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable to aspirin and placebo across eGFR categories with hazard ratios ranging from 0.97 (95% CI, 0.76-1.23) to 1.28 (95% CI, 1.02-1.59) and from 0.75 (95% CI, 0.48-1.17) to 1.34 (95% CI, 0.81-2.22), respectively. CONCLUSIONS: The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Obesity and Kidney Function: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Obesity and type 2 diabetes (T2D) are correlated risk factors for chronic kidney disease (CKD). METHODS: Using summary data from GIANT (Genetic Investigation of Anthropometric Traits), DIAGRAM (DIAbetes Genetics Replication And Meta-analysis), and CKDGen (CKD Genetics), we examined causality and directionality of the association between obesity and kidney function. Bidirectional 2-sample Mendelian randomization (MR) estimated the total causal effects of body mass index (BMI) and waist-to-hip ratio (WHR) on kidney function, and vice versa. Effects of adverse obesity and T2D were examined by stratifying BMI variants by their association with WHR and T2D. Multivariable MR estimated the direct causal effects of BMI and WHR on kidney function. The inverse variance weighted random-effects MR for Europeans was the main analysis, accompanied by several sensitivity MR analyses. RESULTS: One standard deviation (SD ≈ 4.8 kg/m2) genetically higher BMI was associated with decreased estimated glomerular filtration rate (eGFR) [ß=-0.032 (95% confidence intervals: -0.036, -0.027) log[eGFR], P = 1 × 10-43], increased blood urea nitrogen (BUN) [ß = 0.010 (0.005, 0.015) log[BUN], P = 3 × 10-6], increased urinary albumin-to-creatinine ratio [ß = 0.199 (0.067, 0.332) log[urinary albumin-to-creatinine ratio (UACR)], P = 0.003] in individuals with diabetes, and increased risk of microalbuminuria [odds ratios (OR) = 1.15 [1.04-1.28], P = 0.009] and CKD [1.13 (1.07-1.19), P = 3 × 10-6]. Corresponding estimates for WHR and for trans-ethnic populations were overall similar. The associations were driven by adverse obesity, and for microalbuminuria additionally by T2D. While genetically high BMI, unlike WHR, was directly associated with eGFR, BUN, and CKD, the pathway to albuminuria was likely through T2D. Genetically predicted kidney function was not associated with BMI or WHR. CONCLUSIONS: Genetically high BMI is associated with impaired kidney function, driven by adverse obesity, and for albuminuria additionally by T2D.

Impact of Removing the Race Coefficient in Renal Function Estimate Equations on Drug Dosage Recommendations.

BACKGROUND: The appropriateness of including the race coefficient in glomerular filtration rate (GFR) equations in Black patients is debated, and the impact on drug dosing is unknown. OBJECTIVE: This study explored the impact of removing the race coefficient on drug dosing in Black patients in comparison to conventional methods. METHODS: This was a retrospective study of hospitalized patients who self-identified as Black/African American and were prescribed an antimicrobial that includes renal dosage recommendations in the product labeling. The primary end point was the discordance between drug dosing recommendations derived by body surface area deindexed GFR estimated by the CKD-EPI equation (Chronic Kidney Disease Epidemiology study) with and without race versus recommendations derived from Cockcroft-Gault (CG). RESULTS: A total of 210 Black patients were included. There was an 18% rate of discordance when GFR was estimated with the race coefficient (GFR w/Race) versus without the race coefficient (GFR w/out Race). GFR w/out Race had a higher level of agreement with dosing by creatinine clearance (CrCl; κ = 0.779) than GFR w/Race versus CrCl (κ = 0.651). GFR w/out Race had less within-patient difference than GFR w/Race in comparison to CrCl (mean difference: -6.3 vs -18.0 mL/min). CONCLUSIONS AND RELEVANCE: This represents the first report to examine the removal of the race coefficient and its implication on drug dose discordance. GFR w/out Race had a higher level of agreement and less drug dose discordance than GFR w/Race, in comparison to CrCl estimates. If GFR equations are considered comparable to CrCl for the purposes of guiding drug dosing, GFR w/out Race should be considered.

Impaired renal clearance among Swedish adolescents born preterm.

AIM: To determine whether adolescents born before 28 gestational weeks have an increased risk for renal impairment. METHODS: Swedish infants, born before 28 gestational weeks in 2001 and 2002, were identified from a local register. A total of 16 children, 12 females and 4 males, were examined at 16-17 years of age with 51 Cr-EDTA clearance. A comparison group (n = 26) was used. RESULTS: Most study participants (n = 13) had normal blood pressure; one individual had hypertension stage 1. All study participants had results within the reference interval for ionised calcium, parathyroid hormone, intact fibroblast growth factor-23 and for urinary albumin-to-creatinine ratio. Four out of 16 participants (25%) had a 51 Cr-EDTA clearance less than 90 ml/min/1.73 m2 , indicating a reduced kidney function. Measured 51 Cr-EDTA clearance values were significantly lower in the study group than in the comparison group (p = 0.0012). Five study participants (31%) were referred for further investigations. CONCLUSION: Swedish children born before 28 gestational weeks have an increased risk of renal impairment later in life, suggesting that the kidney function in these individuals should be assessed, at least once, during adolescence.

Estimation of the glomerular filtration rate in children and young adults by means of the CKD-EPI equation with age-adjusted creatinine values.

The CKD-EPI creatinine-based estimation equation for glomerular filtration rate (GFR) cannot be used in children, overestimates GFR in young adults, and its combination with the KDIGO recommended pediatric CKiD (Schwartz bedside) equation causes implausible increases in estimated GFR when switching from pediatric to adult care. By establishing sex-specific creatinine growth curves for children and young adults, creatinine levels of children and young adults below age 40 years were adjusted with 40 as assigned age and applied in the CKD-EPI equation. Validation was performed in 4005 children (2-17 years) and 3309 young adults (18-39 years) using metrics based on bias, precision, and accuracy including percentage of estimates within 30% (P30) of measured GFR (mGFR). Comparisons were made with the CKiD and Schwartz-Lyon equations in children. CKD-EPI with age-adjusted creatinine instead of actual age and creatinine led to extensive improvements in bias, precision, and accuracy at all ages, in both sexes and at all levels of mGFR. At mGFR below and above 75 mL/min/1.73m2, the P30 increased from 12% to 75% and 33% to 88% in children, respectively, and from 56% to 73% and 83% to 92% in young adults, respectively. In children adjusted CKD-EPI was more accurate than CKiD, especially above mGFR 75 mL/min/1.73m2 (P30 88% vs. 82%), while Schwartz-Lyon was more accurate than adjusted CKD-EPI at mGFR below 75 mL/min/1.73m2 (P30 81% vs. 75%). Thus, the proposed strategy based on age-adjusted creatinine in children and young adults makes the CKD-EPI equation applicable across the full spectrum of age and kidney function.

Diagnostic Test Characteristics of Ultrasound Based Hydronephrosis in Identifying Low Kidney Function in Young Patients with Spina Bifida: A Retrospective Cohort Study.

PURPOSE: Kidney dysfunction in spina bifida is usually detected by low estimated glomerular filtration rate or ultrasound based hydronephrosis. We assessed the diagnostic test characteristics of hydronephrosis for detecting low estimated glomerular filtration rate, hypothesizing that hydronephrosis has low sensitivity compared to cystatin C based estimated glomerular filtration rate. MATERIALS AND METHODS: We conducted a single center, retrospective cohort study, including patients with spina bifida from 2012-2017 with 2 kidneys and complete data needed to calculate estimated glomerular filtration rate via multiple pediatric (age 1-17.9 years) or adult (age ≥18 years) estimating equations. We evaluated the association of hydronephrosis status (high grade, low grade or none) with estimated glomerular filtration rate, adjusting for small kidney size and scarring, and calculated diagnostic test characteristics of hydronephrosis for low estimated glomerular filtration rate. RESULTS: We analyzed 247 patients (176 children and 71 adults). Mean±SD age was 13.7±6.6 years, and 81% of patients had myelomeningocele. Hydronephrosis (77% low grade) was found in 35/176 children and 18/71 adults. Hydronephrosis was associated with low estimated glomerular filtration rate in stepwise fashion, independent of kidney size and scarring. However, across cystatin C based pediatric equations, any hydronephrosis (compared to none) had 23%-48% sensitivity, and high grade hydronephrosis (compared to none or low grade) had 4%-15% sensitivity for estimated glomerular filtration rate <90 ml/min/1.73 m2, which remained unchanged after excluding small kidneys and scarring. Across cystatin C based adult equations, any and high grade hydronephrosis had 55%-75% and 40%-100% sensitivity, respectively, for estimated glomerular filtration rate <90 ml/min/1.73 m2, although with wide confidence intervals. Specificity was higher with high grade vs any hydronephrosis. Sensitivities were higher for estimated glomerular filtration rate <60 ml/min/1.73 m2. CONCLUSIONS: Hydronephrosis was associated with low estimated glomerular filtration rate but had poor sensitivity for cystatin C based estimated glomerular filtration rate <90 ml/min/1.73 m2, especially among children with spina bifida.

Prescribing sodium-glucose co-transporter-2 inhibitors for type 2 diabetes in primary care: influence of renal function and heart failure diagnosis.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are licenced for initiation for glucose lowering in people with type 2 diabetes (T2DM) with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2). However, recent trial data have shown that these medications have renal and cardio-protective effects, even for impaired kidney function. The extent to which trial evidence and updated guidelines have influenced real-world prescribing of SGLT-2is is not known, particularly with co-administration of diuretics. METHODS: We performed a cross-sectional analysis of people with T2DM registered with practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database on the 31st July 2019. We calculated the percentage of people prescribed SGLT-2is according to eGFR categories (< 45, 45-59, and ≥ 60 mL/min/1.73m2), with a heart failure diagnosis and stratified by body mass index categories (underweight, normal weight, overweight, obese), and with concomitant prescription of a diuretic. Multilevel logistic regression analysis was performed to determine whether heart failure diagnosis and renal function were associated with SGLT-2i prescribing. RESULTS: From a population of 242,624 people with T2DM across 419 practices, 11.0% (n = 26,700) had been prescribed SGLT-2is. The majority of people initiated SGLT-2is had an eGFR ≥ 60 mL/min/1.73m2 (93.2%), and 4.3% had a heart failure diagnosis. 9,226 (3.8%) people were prescribed SGLT-2is as an add-on to their diuretic prescription. People in the highest eGFR category (≥ 60 mL/min/1.73m2) were more likely to be prescribed SGLT-2is than those in eGFR lower categories. Overweight (OR 2.05, 95% CI 1.841-2.274) and obese people (OR 3.84, 95% CI 3.472-4.250) were also more likely to be prescribed these medications, whilst use of diuretics (OR 0.74, 95% CI 0.682-0.804) and heart failure (OR 0.81, 95% CI 0.653-0.998) were associated with lower odds of being prescribed SGLT-2is. CONCLUSIONS: Prescribing patterns of SGLT-2is for glucose lowering in T2DM in primary care generally concur with licenced indications according to recommended renal thresholds. A small percentage of people with heart failure were prescribed SGLT-2is for T2DM. An updated analysis is merited should UK National Institute for Health Care and Excellence prescribing guidelines for T2DM be revised to incorporate new data on the benefits for those with reduced renal function or with heart failure.

Pro-Enkephalin and its association with renal function in Middle Eastern immigrants and native Swedes.

Iraqi-born immigrants residing in Sweden exhibit lower blood pressure as well as better renal function despite an overall worse metabolic risk profile in comparison with native Swedes. This may indicate the presence of cardiorenal protective mechanisms in the Middle Eastern population. Hence, the aim of this study was to investigate whether the association between renal function and Pro-Enkephalin (PENK), a biomarker predictive of both acute and chronic kidney dysfunction, differs across ethnicities. The MEDIM population-based study including a cohort of women and men, born in Iraq or Sweden, aged 30-75 years was conducted in Malmö, Sweden, from 2010 to 2012. The study included fasting blood samples, physical examinations and self-administrated questionnaires. Despite significantly better renal function assessed by creatinine-based eGFR in the Iraqi group, levels of PENK did not differ between the groups, (70.0 pmol/L, born in Iraq (n = 1263) vs 71.1, born in Sweden (n = 689), p = .4). However, the association between PENK and renal function was relatively weaker in the Iraqi born group, as supported by a significant interaction between PENK and country of birth (PInteraction= Country of birth x PENK = 0,010). This observational study suggests that the association between renal function and PENK was weaker in Middle Eastern immigrants. This is of interest as PENK may exhibit a direct effect on renal function, however further research is needed including studies on causality.

Distribution of creatinine and estimated glomerular filtration rate in healthy schoolchildren: The Health Oriented Pedagogical Project (HOPP).

Glomerular filtration rate (GFR) measured by urinary clearance of inulin is considered the gold standard for assessment of kidney function in both adults and children. Because the procedure is cumbersome, GFR is estimated (eGFR) using algorithms based on the observed relationship between measured GFR (mGFR) and more accessible biomarkers such as creatinine and cystatin C. In children, most of the data on this relationship is retrieved from patients with reduced kidney function. Nonetheless, eGFR equations are widely in use in healthy children to evaluate kidney status and diagnose kidney disease. The aim of the present study was to compare the distribution of eGFR using two established pediatric eGFR equations incorporating age, height and serum creatinine (Schwartz-Lyon and Full Age Spectrum-height) and two recently published equations restricted to age and serum creatinine (Lund-Malmö Revised 18 and European Kidney Function Consortium equation) in 1200 healthy schoolchildren age 6-12 years. In addition, we present 2.5th, median and 97.5th percentiles for serum creatinine stratified by age and gender. Depending on the equation used, mean eGFR ranged from 101.6 to 115.4 mL/min/1.73 m2. The lower 2.5th percentile ranged from 83.3 to 89.0 mL/min/1.73 m2 and the fraction of children with eGFR < 90 mL/min/1.73 m2 ranged from 2.9% to 9.8%. In conclusion, expected values of eGFR in healthy children are significantly dependent on the equation used. When decision limits for diagnosis or classification are applied to eGFR results, the related equation should be clearly stated.

Clinical advantages of robot-assisted partial nephrectomy versus laparoscopic partial nephrectomy in terms of global and split renal functions: A propensity score-matched comparative analysis.

OBJECTIVES: To identify predictors of renal function preservation, and to compare the global and split renal function outcomes of robot-assisted partial nephrectomy and laparoscopic partial nephrectomy. METHODS: Demographic, operative and pathological data, as well as renal function outcomes, of 251 patients who underwent laparoscopic (n = 104) and robot-assisted (n = 147) partial nephrectomy between 2008 and 2018 were retrospectively analyzed. Propensity score matching (1:1) was carried out to adjust for potential baseline confounders. Functional outcomes were assessed based on the estimated glomerular filtration rate and dynamic renal scintigraphy (using 99m Tc-mercaptoacetyltriglycine), including renal volumetric analysis. RESULTS: A total of 98 patients were allocated to each partial nephrectomy group. Ischemic (laparoscopic vs robot-assisted partial nephrectomy: 29 vs 15 min, P < 0.001) and operative times (181 vs 100 min, P < 0.001) were shorter in robot-assisted partial nephrectomy. The preservation ratio of global renal function at 3 months (88.3% vs 91.4%, P = 0.040) and 12 months (87.8% vs 91.5%, P = 0.010) postoperatively, and the renal function of the operated kidney (80.3% vs 88.2%, P < 0.001) were greater after robot-assisted partial nephrectomy. In robot-assisted partial nephrectomy, the volume of resected parenchyma was significantly smaller (27.2 vs 15.5 mL, P < 0.001), resulting in greater postoperative normal parenchymal volumes (120 vs 132 mL, P < 0.001) and a greater parenchymal preservation ratio (81.1% vs 90.1%, P < 0.001). The parenchymal preservation ratio was the strongest predictor of renal function preservation after surgery (P < 0.001, odds ratio 6.02). CONCLUSIONS: Robot-assisted partial nephrectomy allows better preservation of split renal function than laparoscopic partial nephrectomy by increasing the parenchymal preservation ratio. This translates into better postoperative global renal function.

Clinical and radiographic outcomes following salvage intervention for ureteropelvic junction obstruction.

PURPOSE: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). MATERIALS AND METHODS: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. RESULTS: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. CONCLUSIONS: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.